This research will define the mechanisms by which experimental neoplasms induce "regional lymph node paralysis" and apply this information in preventing postsurgical metastases. Our pilot studies indicate that MCA-3 sarcoma grows only as a local tumor in normal rats. Amputation of the tumor-bearing limb with excision of the inguinal nodes results in metastases to the para-aortic nodes and lung, but partial excision of the primary fails to induce tumor spread. Sarcoma growth is inhibited in secondary recipients when regional node cells are added to the MCA-3 inoculum while distant node cells lack comparable suppressor activity. These results suggest that "paralysis" may reflect immune responses to TSTA which perturb lymphocyte traffic in the node and sequester antigen reactive cells causing relative depletion of this population in other tissues. The proposed studies will utilize regional arterial dye infusions, histology and radiotracer techniques to describe microvascular, parenchymal and cell traffic changes in regional nodes draining local sarcomas and para-aortic nodes developing metastases after surgery. Selective recruitment of tumor specific lymphocytes will be evaluated by comparing the uptake of immune and non-immune lymphocytes labeled with 3H and 14C-thymidine in regional and contralateral nodes. Tumor transfer assays will compare the ability of lymphocyte and macrophage populations from these nodes to suppress sarcoma growth. Experiments combining excision of primary tumors and/or regional nodes with re-infusion of the nodal cells will determine if draining lymph nodes function as immunologic barriers to intralymphatic metastases. The final studies will establish whether selected adjuvants or pharmacologic mobilization of lymph node cells during surgery prevent tumor spread.